Genotoxic and cytotoxic potential of Alternanthera Bettzickiana, an important ethno-medicinal plant.

The present study was carried out to investigate the mutagenic and cytotoxic potential of n-hexane and aqueous-methanolic whole plant extracts of Alternanthera bettzickiana. Aqueous-methanolic and n-hexane extracts of Alternanthera bettzickiana extracts were assessed for the mutagenic potential with Salmonella tester strains TA-100 and TA-102 in the presence and absence of the rodent enzyme activation system and cytotoxic potential was assessed by MTT assay. Aqueous-methanolic extract showed the presence of saponins, tannins, terpenoids, flavonoids and glycosides. However n-hexane extract revealed the presence of tannins and terpenoids only. It was found that a concentration as low as 15mg/mL of both extracts was more mutagenic to the TA 102 tester strain than TA-100. Hexane whole plant extract of Altenanthera bettzickiana was more mutagenic than aqueous-methanolic extract considering revertant colonies of TA 100 strain. Aqueous-methanolic and n-hexane whole plant extracts of Altenanthera bettzickiana showed higher mutagenic potential in the presence of the enzyme activation system. Mutagenicity of aqueous-methanolic extract increased with an enzyme activation system in case of TA 100 whereas mutagenicity of n-hexane extract decreased in the presence of the enzyme activation system with TA 100 and TA 102 strains. Aqueous-methanolic and n-Hexane whole plant extracts of Alternanthera bettzickiana showed an IC-50 of 493 and 456 µg/mL in BHK-21 cells respectively. It can be concluded that Altenanthera bettzickiana exhibited mutagenic activity in a bacterial reverse mutation assay with and without enzyme activation systems. However, it showed limited cytotoxicity to BHK-21 cells.

Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

Hour-to-hour variability of oxygen saturation in sleep apnea.

STUDY OBJECTIVES: Methods used to express the severity of oxygen desaturation during polysomnography include the average oxygen saturation (AO2), lowest oxygen saturation (LO2), and the percent of the total time with oxygen saturation level lower than 90% (T<90%). We wanted to determine which one of these methods is least variable during different hours of monitoring. DESIGN: Prospective, observational study. SETTING: Sleep center at a medical university. PATIENTS: One hundred fifty patients with apnea-hypopnea index from 5 to 130. MEASUREMENTS: AO2, LO2, and T<90% were calculated during each of the 8 h of polysomnography. Data for each hour were compared and the Cronbach alpha coefficients were calculated. RESULTS: There was a high degree of correlation among the three methods as well as between each method and the severity of sleep apnea. The mean+/-SD values for each method were as follows: AO2, 92.7+/-5.6; LO2, 68.5+/-19.3; and T<90%, 15.7+/-24.2. The alpha coefficients for these methods were AO2, 0.98; LO2, 0.88; and T<90%, 0.98. In all methods, the data of the first hour were significantly different from the data of the subsequent hours. CONCLUSION: Both AO2 and T<90% methods show less hour to hour variability compared with LO2, and there is more variability in the first hour. Since the AO2 values >90% may not convey the severity of O2 desaturation, T<90% may be the best method of expressing oxygen saturation changes during polysomnography.

Intracranial hemodynamics in sleep apnea.

Intracranial pressure changes and poor cerebral perfusion have been reported in sleep apnea syndrome (SAS), but such studies have been limited due to lack of a reliable noninvasive study method. We determined the systolic (VS), diastolic (VD), and mean (VM) cerebral blood flow velocities of the middle cerebral artery in 23 individuals (12 severe SAS patients and 11 control subjects) using transcranial Doppler sonography before sleep, during sleep (NREM and REM) and upon awakening. All three velocities (VS = 87.4 cm/s compared to 104.7 cm/s, VD = 41.6 cm/s compared to 47.7 cm/s, and VM = 57.0 cm/s compared to 67.0 cm/s) were decreased in patients with SAS and VS and VM were significantly lower than in control subjects (p = 0.005 and p = 0.033, respectively). The end-tidal CO2 (PETCO2) in the SAS patients (47.3 mm Hg) compared to the control subjects (41.8 mm Hg) was significantly higher (p = 0.003). When the VM was adjusted to normalized CO2 using the Markwalder's equation, the reduction in velocity in patients with SAS (47.5 cm/s) compared to control subjects (63.0 cm/s) became more significant (p = 0.005). This study shows that cerebral blood flow velocities are lower in patients with SAS compared to control subjects and that transcranial Doppler sonography may be useful in such evaluations.

The effect of sleep on intracranial hemodynamics: a transcranial Doppler study.

The effect of sleep on intracranial blood flow velocities has not been reported in children or adults, even though blood flow velocities are evaluated for clinical purposes during both sleep and wakefulness. We report the effect of sleep on intracranial blood flow velocities of 11 healthy individuals (five children and six adults) who were monitored by polysomnography and transcranial Doppler sonography (TCD). Thirty-three TCDs were obtained on middle cerebral arteries. Before sleep, during non-rapid-eye-movement sleep, and after sleep, measurements of systolic, end diastolic, and mean flow velocities were obtained by TCD. Pulse oximetry and end tidal carbon dioxide were monitored during each 8-hour polysomnogram. The before-sleep blood flow velocity values were compared to sleep and after-sleep values in children and adults separately using ANOVA. A significant decrease in the blood flow velocities was noted during sleep compared to before-sleep values in both children (P less than .05) and adults (P less than .01). The blood flow velocities after sleep were also decreased compared to before-sleep values. This study shows that sleep reduces blood flow velocities in both children and adults. A decrease in blood flow velocities during normal sleep should be taken into account when interpreting TCDs in patients.

Incidence of renal amyloidosis in pulmonary tuberculosis.

Incidences of renal amyloidosis were studied in patients who were in various stages of pulmonary tuberculosis and a three year follow-up gave some opportunity to study the effectiveness of anti-tuberculosis treatment on the course of renal amyloidosis. It was concluded that 9 to 11 per cent of all patients with pulmonary tuberculosis will eventually develop proteinuria due to renal amyloidosis after a certain period of time. It has been postulated that once amyloidosis has extensively involved the kidneys, anti-tuberculous treatment will not cause any regression in the course of renal amyloidosis.

Epidemics of haemorrhagic cystitis due to influenza A virus.

The present communication describes studies on thirty-three patients with haemorrhagic cystitis. The current epidemic variant of influenza type A virus, A/Tehran/5/75 (H3N2) [antigenically similar to A/Port Chalmers/1/73 (H3N2)], was recovered from the throats of eighteen and the urine of three patients. HI antibody rises to A/Tehran/5/75 virus were detected in over 50% of the cystitis patients tested.

Application of gluconolactone in direct tablet compression.

Gluconolactone was evaluated as an excipient for tablets prepared by direct compression using various drugs known to be difficult to compress. The physical properties of the tablets were evaluated after compression and after storage and were satisfactory. Comparative studies were conducted between gluconolactone and anhydrous lactose, a common direct compression diluent, for development of static charges during blending, flow, drug distribution, drug stratification, color distribution, compressibility, and preservation against mold growth. Gluconolactone possesses those properties necessary to produce high quality tablets by the direct compression process. Separate powdered mixtures of aspirin USP with gluconolactone, anhydrous lactose, spray-dried lactose, mannitol, and sorbitol were stored at various humidities and temperatures for specified periods and tested for the integrity of aspirin. Gluconolactone contributed least to the degradation of the drug as compared to other excipients studied. A preliminary in vivo study also was conducted on the bioavailability of aspirin from separate and similar mixtures with gluconolactone, anhydrous lactose, and starch. Gluconolactone did not show any inhibitory effect on aspirin absorption.

Prevention of hepatitis type B with specific immune serum globulin.

In order to evaluate the preventive value of specific immune serum globulin against hepatitis type B, we have used this immune globulin in required doses in 12 patients (10 with AU antigen negative and 2 with AU antigen positive) with chronic renal failure who required maintenance hemodialysis for a period of 15 months, and we were able to prevent hepatitis type B in our dialysis patients.

Effect of beta adrenergic blocking agents (alprenolol and propranolol) in essential hypertension.

The antihypertensive effect of two adrenergic blocking agents (Alprenolol and Propranolol) have been studied in a group of 107 patients with essential hypertension. A significant reduction of 20 mmHg in the systolic blood pressure was recorded for the group using Alprenolol and 25 mmHg in the group using Propranolol. The corresponding decrease of 7-10 mmHg in the diastolic blood pressure for the entire group was also significant. These two drugs may be of therapeutic value in essential hypertension, independently or in combination with other antihypertensive drugs.